INVIVO AND INVITRO STUDIES ON THE EFFECT OF AMPHOTERICIN-B ON ENDOTHELIN RELEASE

Since amphotericin B nephrotoxicity is mediated, in part by hypoxic tubular injury, the role of endothelin in the renal vasoconstriction, characteristic of amphotericin toxicity has been studied. Intact and salt depleted rats were infused with amphotericin B (20 μg/lcg per min) or 5% dextrose over 20 min. Plasma endothelin levels determined at the conclusion of the infusion period, did not differ between the experimental groups, despite a marked reduction in renal blood flow noted in rats infused with amphotericin B. Amphotericin B (10-5-10-7 m) did not stimulate endothelin release from cultured bovine aortic endotheh'al cells. However, in a model of chronic amphotericin nephrotoxicity produced by repeated daily intraperitoneal injections of amphotericin B (5 mg/kg) to salt depleted rats, renal failure was associated with elevated plasma endothelin levels (29·3 ± 4·4 fmol/mL, vs 10·8 ±1·2 fmol/mL in salt depleted controls, P <0·01). We conclude that while plasma endothelin may be increased in chronic amphotericin B nephropathy, this peptide does not mediate the acute renal vasoconstriction associated with the infusion of this drug. © 1992 by The British Society for Antimicrobial Chemotherapy.